Zhang R, Kyriss T, Dippon J, Hansen M, Boedeker E, Friedel G. American Society of Anesthesiologists physical status facilitates risk stratification of elderly patients undergoing thoracoscopic lobectomy. Eur J Cardiothorac Surg. 2018;53(5):973-979.
Cite this article as: Zhang R, Kyriss T, Dippon J, Hansen M, Boedeker E, Friedel G. American Society of Anesthesiologists physical status facilitates risk stratification of elderly patients undergoing thoracoscopic lobectomy. Eur J Cardiothorac Surg 2018;53:973–9.
American Society of Anesthesiologists physical status facilitates risk stratification of elderly patients undergoing thoracoscopic lobectomy
Ruoyu Zhanga,*, Thomas Kyrissa, Ju¨rgen Dipponb, Matthias Hansenc, Enole Boedekeraand Godehard Friedela
a Department of Thoracic Surgery, Center for Pneumology and Thoracic Surgery, Chest Hospital Schillerhoehe, Robert-Bosch-Krankenhaus, Teaching Hospital of the University of Tuebingen, Stuttgart, Germany
b Institue of Stochastics and Applications, Department of Mathematics, University Stuttgart, Stuttgart, Germany
c Department of Anesthesia, Chest Hospital Schillerhoehe, Robert-Bosch-Krankenhaus, Teaching Hospital of the University of Tuebingen, Stuttgart, Germany
* Corresponding author. Department of Thoracic Surgery, Center for Pneumology and Thoracic Surgery, Schillerhoehe Hospital, Solitudestrasse 18, Stuttgart/
Gerlingen, Germany. Tel: +49-7156-2037731; fax: +49-7156-2032024; e-mail: ruoyu.zhang@klinik-schillerhoehe.de (R. Zhang).
Received 5 April 2017; received in revised form 6 November 2017; accepted 12 November 2017
Abstract
OBJECTIVES:Accurate risk assessments are particularly important for elderly patients being considered for lobectomy. Considering the positive effects of the thoracoscopic approach on postoperative outcomes, we sought to review the reliability of the established risk factors for elderly patients undergoing thoracoscopic lobectomy.
METHODS:From January 2009 to March 2016, 441 patients in our institution underwent thoracoscopic lobectomy for early-stage lung cancer. Clinical outcomes were compared between elderly (>70 years,n= 176) and younger patients (n= 265).
RESULTS: There was no significant difference in postoperative mortality and morbidity between elderly and younger patients. In the regression analyses restricted to elderly patients, American Society of Anesthesiologists physical status (ASA-PS) was the single strong pre-dictor of postoperative morbidity. The odds of pulmonary and cardiopulmonary complications increased nearly 6- and 3-fold, respect-ively, in those with ASA-PS Grade 3 compared with patients with ASA-PS Grade <3. Additionally, male gender was found to have a possible causal effect of pulmonary complication in elderly patients. After confounder adjustment using propensity score matching, the generalized linear mixed model revealed more than an 8-fold increase in the odds of pulmonary complications in elderly men compared with elderly women. To check the robustness of the above-mentioned finding, inverse probability of treatment weighting was used as an alternative analysis indicating a weaker but still substantively significant effect of male gender, with an odds ratio >3.
CONCLUSIONS:Our results suggest that ASA-PS is a strong predictor of morbidity among elderly patients considered for thoracoscopic lobectomy. Compared with elderly women, elderly men are particularly prone to postoperative pulmonary complications.
Keywords: Elderly • Risk assessment • American Society of Anesthesiologists physical status • Lung resection • Minimally invasive thoracic surgery • Outcomes
INTRODUCTION
The number of elderly patients with early-stage lung cancer is ex-pected to increase rapidly because of the current demographic trends [1]. Increased age is associated with impaired respiratory performance and a greater burden of comorbidities [2,3]. These age-related changes in turn cause a higher risk of postoperative mortality and morbidity following major lung resection [4, 5].
Moreover, elderly patients have limited physiological reserve to cope with the increased stress associated with postoperative complications [6]. Thus, an accurate preoperative risk assessment and careful patient selection are particularly important for this special patient population.
Thoracoscopic lobectomy has been widely adopted in the past decade and is currently the recommended surgical approach for the treatment of early-stage lung cancer. Cumulative evidence
has demonstrated that relative to thoracotomy, thoracoscopic lobectomy results in reduced postoperative mortality and mor-bidity, particularly in high-risk patients, e.g. those with impaired pulmonary function or older age [5,7, 8]. In fact, a propensity score-matched study found a 6-fold decrease in the odds of morbidity in elderly patients after thoracoscopic lobectomy com-pared with an open approach [5]. Accordingly, there is growing interest in the application of this minimally invasive procedure in elderly patients. This development has also raised the important question of the validity of previously published risk assessment models, which are based on clinical data primarily obtained from open lung resections [9]. Given the positive effects of the thoraco-scopic approach on postoperative outcomes, it is reasonable to speculate that the magnitude and the impact of established mor-bidity predictors may be altered in elderly patients undergoing thoracoscopic lobectomy.
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European Journal of Cardio-Thoracic Surgery 53 (2018) 973–979 ORIGINAL ARTICLE
doi:10.1093/ejcts/ezx436 Advance Access publication 8 December 2017
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In this study, we reviewed our institutional database regarding thoracoscopic major lung resection and explored the relation-ships between established predictors and postoperative compli-cations following thoracoscopic lobectomy in elderly patients with early-stage lung cancer.
PATIENTS AND METHODS
A retrospective study was performed using our institutional data-base, which includes retrospective data on thoracoscopic major lung resections from 2009 to 2014 and prospective data there-after. All adult patients undergoing thoracoscopic lobectomy for early-stage non-small-cell lung cancer were included in this study. Patients older than 70 years were considered elderly, be-cause the age of 70 is usually considered the lower boundary of senescence [10]. In fact, organ dysfunction and comorbid condi-tions increase sharply after this age [3]. We compared the clinical outcomes of elderly patients with those of younger patients. This study was approved by the local institutional review board, and specific patient consent was waived.
All patients received computed tomography and positron emission tomography scans as well as brain magnetic resonance imaging to screen for regional and distal metastases. Patients with suspected mediastinal nodal metastases underwent endo-bronchial ultrasound-guided fine-needle aspiration or transcervi-cal mediastinoscopy. Intensive assessment of clinitranscervi-cal history, physiological evaluation and laboratory tests were obtained in all patients prior to surgery. Performance status of patients was con-sidered marginal or poor for an Eastern Cooperative Oncology Group (ECOG) scale >_2. The predicted postoperative value of forced expiratory volume in 1 s expressed as the percent
predicted (ppoFEV1%) and the diffusing capacity of the lung ex-pressed as the percent predicted (ppoDLCO%) were calculated using the functional segment technique; in this technique, pre-operative FEV1% or DLCO% was multiplied by the fraction of the functional lung segments expected to remain after lobectomy [9].
All patients with preoperative lung function testing that demon-strated impaired pulmonary function (ppoFEV1% or ppoDLCO%
<40) were submitted to a stair-climbing test or cardiopulmonary exercise testing (cycle ergometry) as additional risk stratification measures prior to lobectomy. When the performance of the pa-tients on the stair-climbing test was not satisfactory, cycle ergo-metry was indicated to determine their eligibility. A maximum oxygen consumption greater than 10 ml/kg/min or 35% of pre-dicted was considered sufficient for lobectomy.
Comorbidity was assessed using the Charlson comorbidity index (CCI). In this study, we adopted an updated version of the CCI that encompassed 23 medical conditions, which are sum-marized in Table1[11]. Compared with the original version, the updated version includes 4 more comorbid conditions including hypertension, depression, use of warfarin and skin ulcers/cellulitis and was found to better predict health outcomes in previous analyses of data from the national population health surveys [12].
Because the lung cancer patients involved in this study under-went thoracoscopic lobectomies with a curative intent, lung can-cer was not scored as a malignancy, in accordance with previous reports. Additionally, modifications were made to score coronary artery disease and myocardial infarction together with a value of 1. Moderate or severe comorbidity was indicated when the CCI score was >_3.
All cases were preoperatively reviewed by our multidisciplinary lung oncology team, which includes oncologists, respiratory physicians, radiologists, pathologists, nuclear medicine physicians
Table 1: Charlson comorbidity index and prevalence of comorbid conditions
Score Condition Elderly patients (n= 176) Younger patients (n= 265) P-value
Affected,n(%) Affected,n(%)
1 Coronary artery disease/myocardial infarction 39 (22.2) 35 (13.2) 0.010
Congestive heart failure 29 (16.5) 18 (6.8) 0.001
COPD/asthma 52 (29.5) 97 (36.6) 0.15
Hypertension 118 (67.0) 128 (48.3) 0.001
Peripheral vascular disease 29 (16.5) 23 (8.7) 0.016
Mild liver disease 3 (1.7) 5 (1.9) 1.00
Cerebrovascular disease 22 (12.5) 24 (9.1) 0.27
Connective tissue disease 2 (1.1) 7 (2.6) 0.33
Diabetes without end-organ damage 37 (21.0) 25 (9.4) 0.001
Dementia 0 0
Depression 5 (2.9) 9 (3.4) 1.00
Ulcer disease 12 (6.8) 13 (4.9) 0.41
Takes warfarin 17 (9.7) 8 (3.0) 0.005
2 Hemiplegia 1 (0.6) 1 (0.4) 1.00
Moderate-to-severe renal disease 8 (4.5) 5 (1.9) 0.15
Diabetes with end-organ damage 2 (1.1) 0 0.16
Any prior tumour (within 5 years of the diagnosis)a 27 (15.3) 32 (12.1) 0.32
Skin ulcers/cellulitis 0 0
Leukaemia 0 1 (0.4) 1.00
Lymphoma 6 (3.4) 3 (1.1) 0.17
3 Moderate-to-severe liver disease 0 1 (0.4) 1.00
6 Metastatic solid tumour 2 (1.1) 0 0.16
HIV/AIDS 0 0
aExcept basal cell skin carcinoma.
AIDS: acquired immune deficiency syndrome; COPD: chronic obstructive pulmonary disease; HIV: human immunodeficiency virus.
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and thoracic surgeons. As a measure of overall health status, the American Society of Anesthesiologists physical status (ASA-PS) was determined by the responsible anaesthesiologists for all pa-tients prior to surgery according to the modern version [13].
Lung cancer staging was performed according to the American Joint Committee on Cancer seventh edition manual [14].
Pathological stage was reported based on the final histopatho-logical findings after lobectomy and radical mediastinal lymph node dissection.
In our institution, thoracoscopic lobectomy is performed using a 3-port approach, including a 3-cm anterolateral access incision in the fourth intercostal space without rib spreading and with visualization through the monitor only. Lobar vessels and the bronchus are individually ligated, and the hilar and the medias-tinal lymph nodes are dissected.
Mortality was defined as death during hospitalization for thor-acoscopic lobectomy or within 30 days of the operation.
Postoperative complications were defined according to the Society of Thoracic Surgeons and the European Society of Thoracic Surgeons (STS/ESTS) joint standardization of variable definitions and terminology [15]. Pulmonary complications included pneumonia, atelectasis requiring bronchoscopy, adult respiratory distress syndrome, initial ventilator support >48 h and unplanned reintubation or tracheotomy. Cardiovascular compli-cations were defined as acute myocardial infarction, pulmonary embolism and atrial or ventricular arrhythmia requiring interven-tion. All other adverse events including postoperative bleeding, wound infection, recurrent laryngeal nerve injury, bronchopleu-ral fistula and other relevant events were defined as ‘other major complications’. Although postoperative bleeding and recurrent laryngeal nerve injury result mostly from technical complications, we considered them to be other major complications because they are commonly associated with other serious adverse events.
Overall morbidity was defined as the occurrence of any major complication including mortality.
Statistical analysis
Categorical variables were expressed as percentages and were evaluated with the Fisher’s exact test. Continuous data were pre-sented as the median and interquartile range and were com-pared using the Wilcoxon rank-sum test. Logistic regression analyses were performed to explore the relationships between established risk factors and postoperative complications in eld-erly patients. The variables included were gender (male), ppoFEV1%, ppoDLCO%, CCI score (3 vs <3), ECOG performance status (>_2 vs <2) and ASA-PS scale (3 vs <3). While ppoFEV1% and ppoDLCO% were modelled as continuous variables, the remain-ing variables were modelled as binary categorical variables. To evaluate the causal effect of gender on postoperative pulmonary complications in elderly patients, the nearest neighbour propen-sity score matching with replacement was used to establish male and female elderly patients with balanced demographics and clinical characteristics. To estimate the size of the causal effect, generalized linear mixed model with random effects was fitted.
Because matching might introduce a dependency structure, each male patient together with all of his matched female counterparts were considered as an individual group and associated with a random intercept in the logistic regression model. To account for the fact that a male patient could be matched to more than 1 female patient, the reciprocal number of this male patient’s
drawings was used as a weight, whenever this male patient occurred in the matched data set. To evaluate the robustness of the above approach, propensity score adjustment using inverse probability of treatment weighting was performed. In this method, a weight was calculated for each subject that was equal to the inverse of the estimated probability of receiving the treat-ment (gender) that was actually received, conditionally on the observed covariates. These weights were then incorporated into a logistic regression model to estimate the effect of gender on the outcome variable [16]. Statistical significance was determined by aP-value <0.05. Propensity score matching and analysis using generalized linear mixed model, as well as inverse probability of treatment weighting, were conducted using R Project for Statistical Computing, version 3.3.3, along with R package
‘MatchIt’ version 2.4–22, ‘lme4’ version 1.1–13 and ‘ipw’ 1.0–11 [17–20]. The other statistical analyses were performed using SPSS, version 16.0 for Windows (SPSS, Chicago, IL, USA).
RESULTS
From 2009 through March 2016, 441 patients underwent thora-coscopic lobectomy for clinical early-stage non-small-cell lung cancer at our institution. There were 191 women and 250 men, with a median age of 68 (61–74) years. In 12 (2.7%) patients, the thoracoscopic approach had to be converted to open thoracot-omy to complete the lobectthoracot-omy. Impaired pulmonary function (ppoFEV1% or ppoDLCO% <40) was observed in 113 patients in the entire cohort. Of these patients, 49 underwent cycle ergome-try with maximum oxygen consumption measurements ranging from 10.9 to 27.0 ml/kg/min (43.0–162.0%). Pathological analysis indicated Stage I in 341 (77.3%) patients, Stage II in 67 (15.2%) patients and Stage III in 33 (7.5%) patients.
Of the included patients, 176 were elderly and 265 were younger. Patient demographics and clinical characteristics are provided in Table2. Compared with younger patients, elderly pa-tients were more likely to be men. Moderate or severe comor-bidity (CCI >_3) and severe systemic disease (ASA-PS Grade 3) were more likely in elderly patients. No patients had an ASA-PS scale >3. The incidences of each comorbid condition are sum-marized in Table 1. The most common comorbid conditions were hypertension and chronic pulmonary disease, followed by cardiac disease and diabetes without end-organ damage. Two patients had a history of metastatic solid tumour: 1 patient with breast cancer and solitary cerebellar metastasis and the other with prostate cancer and a bony metastasis. Both patients received treatment with a curative intent and were disease-free from prior tumours. Compared with younger patients, elderly pa-tients were more likely to have hypertension, diabetes and car-diovascular disease.
Four postoperative deaths (0.9%) occurred in the entire patient cohort. Three patients died from postoperative pneumonia, while 1 patient developed bronchopleural fistula, followed by multiple organ failure and died on postoperative Day 12. Postoperative pulmonary and cardiovascular complications and overall mor-bidity occurred in 36 (8.2%), 24 (5.4%) and 105 (23.8%) patients, respectively. The rates of postoperative complications including mortality in both groups are depicted in Table3. Elderly patients had higher postoperative complication rates than younger pa-tients. However, these differences did not reach statistical signifi-cance. There was a trend towards a higher pulmonary complication rate in elderly patients (P= 0.052). In the univariable
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logistic regression analyses restricted to elderly patients, postop-erative complications were not related to ppoFEV1%, ppoDLCO%, moderate or severe comorbidity (CCI >_3) or worse performance status (ECOG >_2, Table4). In contrast, more than a 6-fold increase in the odds of pulmonary complications was observed in elderly male patients compared with their female counterparts. In addition, the ASA-PS was the only strong pre-dictor of pulmonary and cardiopulmonary complication rates and overall morbidity. Compared with patients with ASA-PS Grade <3, the odds of pulmonary and cardiopulmonary compli-cations increased nearly 6-fold and 3-fold, respectively, in those with an ASA-PS Grade 3. Because of the limited postoperative adverse events and concern about misleading results, multivari-able logistic regression analysis was not performed.
To further explore the causal effect of gender on postoperative pulmonary complications in elderly patients, propensity score matching was used to identify male and female elderly patients with balanced demographics and clinical characteristics. Of the 176 elderly patients, there were 111 men and 65 women.
Compared with elderly women, elderly men had significantly lower ppoDLCO% values and were significantly more likely to have a history of smoking and moderate or severe comorbidity (Table 5). Additionally, there was a moderate trend towards a lower ppoFEV1% and a higher incidence of overweight in elderly male patients. Accordingly, propensity scores were assessed using a multivariable logistic regression model, which included over-weight (body mass index >_25 kg/m2 vs <25 kg/m2), history of smoking, ppoFEV%, ppoDLCO%, CCI (>_3 vs <3) and pathological Table 2: Patient demographics and clinical characteristics
Variables Elderly patients (n= 176) Younger patients (n= 265) P-value
Affected Affected
Age (years), median (IQR) 76.0 (73.0–80.0) 62.0 (56.0–67.0) <0.001
Male,n(%) 111 (63.1) 139 (52.5) 0.031
Overweight (BMI >_25 kg/m2),n(%) 77 (43.8) 126 (47.5) 0.44
Smoker,n(%) 120 (68.2) 203 (76.7) 0.12
CCI >_3,n(%) 97 (55.1) 107 (40.4) 0.003
ASA-PS Grade 3,n(%) 93 (52.8) 75 (28.3) <0.001
ECOG >_2,n(%) 3 (1.7) 6 (2.3) 1.00
FEV1%, median (IQR) 72.9 (64.7–80.2) 73.6 (64.0–80.8) 0.65
ppoFEV1%, median (IQR) 58.1 (51.3–67.3) 58.0 (51.6–65.8) 0.66
DLCO%, median (IQR) 64.5 (54.5–79.1) 64.8 (50.5–79.1) 0.77
ppoDLCO%, median (IQR) 51.3 (43.7–63.2) 50.8 (39.6–63.7) 1.00
Pathological stage,n(%) 0.29
I 136 (77.3) 205 (77.4)
II 29 (16.5) 38 (14.4)
III 11 (6.3) 22 (8.3)
ASA-PS: American Society of Anesthelogists physical status; BMI: body mass index; CCI: Charlson comorbidity index; DLCO%: diffusing capacity of lung ex-pressed as percent predicted; IQR: interquartile range; ppo: predicted postoperative; ECOG: Eastern Cooperative Oncology Group performance status; FEV1%:
forced expiratory volume in 1 s expressed as percent predicted.
Table 3: Surgical outcomes of thoracoscopic lobectomy in elderly and younger patients
Outcomes Elderly patients (n= 176) Younger patients (n= 265) P-value
Affected,n(%) Affected,n(%)
Postoperative mortality 3 (1.7) 1 (0.4) 0.31
Pulmonary complications 20 (11.4) 16 (6.0) 0.052
Pneumonia 16 (9.1) 12 (4.5) 0.072
Atelectasis requiring bronchoscopy 4 (2.3) 3 (1.1) 0.45
Adult respiratory distress syndrome 3 (1.7) 2 (0.8) 0.39
Initial ventilator support >48 h 4 (2.3) 2 (0.8) 0.22
Unplanned reintubation or tracheotomy 9 (5.1) 4 (1.5) 0.041
Cardiovascular complications 13 (7.4) 11 (4.2) 0.20
Acute myocardial infarction 1 (0.6) 1 (0.4) 1.00
Pulmonary embolism 0 0 –
Atrial arrhythmia 10 (5.7) 10 (3.8) 0.359
Ventricular arrhythmia 3 (1.7) 1 (0.4) 0.307
Other major complications 29 (16.5) 35 (13.2) 0.34
Postoperative bleeding 4 (2.3) 6 (2.3) 0.70
Wound infection 0 1 (0.4) 1.00
Recurrent laryngeal nerve injury 5 (2.8) 3 (1.1) 0.28
Bronchopleural fistula 2 (1.1) 6 (2.3) 0.49
Other relevant events 21 (11.9) 24 (9.1) 0.34
Overall morbidity 47 (26.7) 58 (21.9) 0.26
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stage (advanced vs early). Because of very different distribution of propensity scores in 2 groups, the nearest neighbour propen-sity score matching with replacement was performed. The matching established 2 well-balanced groups consisting of 29 male and 65 female elderly patients (Table6). After the matching process, the pulmonary complication rate was significantly higher in elderly male patients than in their female counterparts (20.7%
vs 3.1%,P= 0.010). Our analysis of matched data using general-ized linear mixed model indicated that male gender was associ-ated with more than an 8-fold increase in the odds of pulmonary complications [odds ratio (OR) 8.591, 95% confidence interval 1.284–57.456; P= 0.027]. To evaluate the robustness of the above-mentioned results, we additionally performed propensity score adjustment using inverse probability of treatment weight-ing, which revealed more than a 3-fold increase in the odds of pulmonary complications in elderly male patients compared with
elderly female patients (OR 3.290, 95% confidence interval 1.531–7.738,P= 0.004).
COMMENTS
The proportion of elderly patients with lung cancer increases as the population ages. Compared with younger patients, elderly patients are more likely to have higher comorbidity burden and worse physical status; these trends were reflected in our analyses of preoperative clinical characteristics. Despite the exposure to these risk factors, thoracoscopic lobectomy resulted in low mor-tality and reasonable morbidity in our elderly patient cohort. Our data support those of previously reported smaller series, which indicated that thoracoscopic lobectomy is safe and justifiable for elderly patients with early-stage lung cancer [21,22].
Table 4: Results of univariable logistic regression analyses of established risk factors for postoperative complications in elderly patients (n= 176)
Pulmonary complication Cardiopulmonary complication Overall morbidity
OR 95% CI P-value OR 95% CI P-value OR 95% CI P-value
Gender (male) 6.663 1.513–29.355 0.012 1.965 0.796–4.850 0.14 1.121 0.570–2.203 0.74
ppoFEV1% 0.976 0.937–1.016 0.24 0.996 0.962–1.030 0.79 0.979 0.951–1.007 0.14
ppoDLCO% 0.974 0.939–1.011 0.17 0.980 0.949–1.012 0.21 0.977 0.951–1.003 0.09
CCI >_3 2.052 0.750–5.616 0.16 1.772 0.748–4.198 0.19 1.138 0.580–2.233 0.71
ECOG >_2 4.053 0.351–46.837 0.26 2.827 0.247–32.31 0.40 1.380 0.122–15.587 0.79
ASA-PS Grade 3 5.965 1.680–21.174 0.006 2.975 1.187–7.454 0.020 2.378 1.176–4.808 0.016
ASA-PS: American Society of Anesthelogists physical status; CCI: Charlson comorbidity index; CI: confidence interval; ECOG: Eastern Cooperative Oncology Group performance status; OR: odds ratio; ppoDLCO%: predicted postoperative diffusing capacity of lung expressed as percent predicted; ppoFEV1%: pre-dicted postoperative forced expiratory volume in 1 s expressed as percent prepre-dicted.
Table 5: Demographic and clinical characteristics of un-matched elderly patients (n= 176), stratified by gender
Variables Male elderly
(n= 111)
Female elderly (n= 65)
P-value
Affected Affected Age (years),
median (IQR)
75.0 (73.0–79.0) 76.0 (73.0–80.0) 0.83 Overweight
(BMI >_25),n(%)
55 (49.5) 22 (33.8) 0.059
Smoker,n(%) 92 (82.9) 28 (43.0) <0.001
CCI >_3,n(%) 70 (63.1) 27 (41.5) 0.007
ECOG >_2,n(%) 3 (2.7) 0 0.30
ppoFEV1%, median (IQR)
57.8 (50.6–62.8) 59.8 (54.1–69.8) 0.069 ppoDLCO%,
median (IQR)
48.7 (39.6–59.2) 55.3 (45.8–65.4) 0.031 Advanced pathologic
stage,n(%)
8 (7.2) 6 (9.2) 0.77
BMI: body mass index; CCI: Charlson comorbidity index; ECOG: Eastern Cooperative Oncology Group performance status; ppoDLCO%: pre-dicted postoperative diffusing capacity of lung expressed as a percent predicted; ppoFEV1%: predicted postoperative forced expiratory vol-ume in the 1 s expressed as percent predicted.
Table 6: Demographic and clinical characteristics of matched elderly patients (n= 94), stratified by gender
Variables Male elderly
(n= 29)
Female elderly (n= 65)
P-value
Affected Affected Age (years),
median (IQR)
76.0 (73.0–78.0) 76.0 (73.0–80.0) 0.82 Overweight
(BMI >_25 kg/m2), n(%)
12 (41.4) 22 (33.8) 0.50
Smoker,n(%) 18 (62.1) 28 (43.0) 0.12
CCI >_3,n(%) 16 (55.2) 27 (41.5) 0.27
ECOG >_2 0 0
ppoFEV1%, median (IQR)
59.2 (52.1–67.7) 59.8 (54.2–69.8) 0.75 ppoDLCO%,
median (IQR)
48.3 (44.6–63.4) 55.3 (45.8–65.4) 0.36 Advanced pathological
stage,n(%)
2 (6.9) 6 (9.2) 1.00
BMI: body mass index; CCI: Charlson comorbidity index; ECOG: Eastern Cooperative Oncology Group performance status; IQR: interquartile range; ppoDLCO%: predicted postoperative diffusing capacity of lung expressed as percent predicted; ppoFEV1%: predicted postoperative forced expiratory volume in 1 s expressed as percent predicted.
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Although an increasing amount of evidence has demonstrated the positive effect of thoracoscopic lobectomy on the postopera-tive outcomes of elderly patients, the authors believe that the fa-vourable outcomes in our elderly patient cohort were also attributable to the thorough risk assessment and careful patient selection performed before surgery. Indeed, both ppoFEV1% and ppoDLCO% in the elderly patients were comparable to those of their younger counterparts. In addition, the majority of our eld-erly patients presented with a good preoperative performance status (ECOG <2). Careful patient selection is one of the most im-portant responsibilities of a surgeon and is particularly imim-portant when the patients are old and present with relevant comorbid-ities [23]. However, from a statistical perspective, our data were affected by substantial selection bias, which may explain why ppoFEV1%, ppoDLCO% and ECOG performance status were not related to postoperative complications.
Interestingly, we found that the ASA-PS was a strong predictor of postoperative adverse outcomes following thoracoscopic lob-ectomy in elderly patients. Compared with elderly patients with an ASA-PS Grade <3, those with an ASA-PS Grade 3 had approxi-mately 6-fold and 3-fold greater odds of pulmonary and cardio-pulmonary complications, respectively. The ASA-PS is a classification system that assesses a patient’s overall health status and degree of sickness. This scale has been widely used by anaes-thesiologists to estimate the operative and anaesthesiological risk. Despite the inherent subjectivity of this scoring system, the predictive ability of the ASA-PS for postoperative complications has been extensively studied and validated in a number of clinical studies. A recent large study involving over 2.3 million patients demonstrated that the ASA-PS has strong, independent associ-ations with postoperative mortality and morbidity [24]. To date, limited data exist regarding the ASA-PS as a predictor of morbid-ity after major lung resection. Only a few prospective studies have identified the ASA-PS as an independent risk factor for postoperative atrial fibrillation and pulmonary complications fol-lowing open lung resection [25, 26]. Notably, the ASA-PS scale has rarely been considered in the risk assessment process prior to major lung resection thus far. Similar to many other centres, in our institution, the ASA-PS was assigned by the responsible an-aesthesiologist 1 day before the scheduled surgery. This informa-tion was usually not available when the treatment decision was made in our multidisciplinary lung oncology team meeting.
Moreover, most lung cancer patients were counselled on the treatment options and risks prior to the anaesthesiologist’s deter-mination of the ASA-PS scale. Based on our findings, assignment of the ASA-PS scale is recommended to be integrated into the preoperative risk assessment for elderly patients who are being considered for thoracoscopic lobectomy. Due to the possible inter-rater inconsistency, especially in assigning Grades 2 (mild systemic disease) and 3 (severe systemic disease), elderly patients with ASA-PS Grade >_2 should consult senior anaesthesiologists as early as possible. We believe that incorporating the ASA-PS will enable more accurate preoperative risk assessments and will fa-cilitate decision-making for this frail patient population.
As a normal part of ageing, elderly patients experience a series of respiratory changes in terms of central regulation, chest wall dy-namics, parenchymal elasticity and gas exchange [2]. This decline in respiratory performance, especially the reduced efficiency in mucociliary transport and the weakening of respiratory muscles, predisposes elderly patients to postoperative pulmonary complica-tions. Notably, the physiological stress caused by postoperative complications is generally poorly tolerated by elderly patients [6].
Because of its minimally invasive nature, thoracoscopic lobectomy is associated with less pain and better preservation of lung func-tion in the initial postoperative period. These advantages then en-able improved deep breathing and early expectoration and ambulation in the postoperative period, which are crucial for eld-erly patients [27]. Accordingly, eldeld-erly patients seem to be among the greatest beneficiaries of thoracoscopic lobectomy [28].
Nevertheless, in this study, we found that there was a trend to-wards a higher pulmonary complication rate in elderly patients when compared with their younger counterparts. With a large enough sample size, the difference in pulmonary complication rates between elderly and younger patients may become signifi-cant. More importantly, our analysis of propensity-matched data using generalized linear mixed model revealed more than an 8-fold increase in the odds of pulmonary complications for elderly male patients compared with their female counterparts.
Interestingly, the alternative analysis using inverse probability of treatment weighting showed a lower OR for pulmonary complica-tion (3.290). However, it is fairly difficult to determine where the discrepancy in the results of the 2 different approaches for causal effect analysis originated from. While propensity score matching with replacement yielded samples with well-balanced baseline characteristics and hence reduced the bias, this advantage was at the cost of a higher variance because of the smaller sample size.
The inverse probability of treatment weighting using propensity score, on the other hand, used all data sets and weighted each subject based on propensity score to control for imbalance. This advantage was reflected in the narrower confidence interval for OR in our analysis. However, this approach might have exagger-ated the importance of the patients with very low propensity score [29]. Nevertheless, both the analysis of propensity-matched data using generalized linear mixed model and the estimation using in-verse probability of treatment weighting indicated a significant ef-fect of male gender on postoperative pulmonary complication in elderly patients undergoing thoracoscopic lobectomy. Our find-ings again highlight the importance of early postoperative pul-monary care and close monitoring of elderly patients undergoing major lung resection, particularly elderly men.
Limitations
This study has certain limitations. As mentioned above, the thor-ough risk assessment and careful patient selection prior to surgery may have caused substantial selection bias. The inherent bias of retrospective data was also of concern. The clinical data on thoraco-scopic lobectomies were prospectively evaluated only in and after 2015. Therefore, it is possible that some postoperative adverse events were undisclosed in patients undergoing thoracoscopic lob-ectomy from 2009 through 2014. Additionally, our results were based on data from a single institution, which may not fully reflect other clinical scenarios. Thus, the general applicability of the findings to other institutions is debatable. Similar studies in other institutions or multicentre studies are warranted to confirm and generalize our findings. Despite the imperfect data, our results may help improve preoperative risk assessments and optimize perioperative manage-ment of elderly patients with early-stage lung cancer.
CONCLUSION
In conclusion, our results suggest that thoracoscopic lobectomy is safe for appropriately selected elderly patients with early-stage
978 R. Zhanget al./ European Journal of Cardio-Thoracic Surgery
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